Myelodysplastic Syndrome Clinical Trial

Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs

Summary

A Phase 3, randomized, open-label, parallel-group, multicenter study designed to evaluate the efficacy and safety of guadecitabine in subjects with MDS or CMML who failed or relapsed after adequate prior treatment with azacitidine, decitabine, or both. This global study will be conducted in approximately 15 countries. Approximately 408 subjects from approximately 100 study centers will be randomly assigned in a 2:1 ratio to either guadecitabine (approximately 272 subjects) or Treatment Choice (approximately 136 subjects). The study consists of a 14-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period. The study is expected to last more than 2 years, and the duration of individual subject participation will vary. Subjects may continue to receive treatment for as long as they continue to benefit.

View Full Description

Full Description

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs Treatment Choice (TC). Approximately 408 participants will be randomly assigned 2:1 to either guadecitabine or TC.

Guadecitabine: approximately 272 participants.
TC: approximately 136 participants.

Before randomization, the investigator will assign each participant to one of the following TC options:

Low dose cytarabine (LDAC).
Standard Intensive Chemotherapy (IC) of a 7+3 regimen.
Best Supportive Care (BSC) only. BSC will be provided to all participants as per standard and institutional practice. Participants randomized to TC will not be allowed to cross over to guadecitabine. Data will be reviewed by an independent Data Monitoring Committee at regular intervals, primarily to evaluate safety during study conduct. Randomization will be stratified by disease category (MDS vs CMML), bone marrow (BM) blasts (BM blasts >10% vs BM blasts ≤10%), TC option (LDAC vs IC vs BSC), and study center region.

Guadecitabine: 60 milligrams per square meter (mg/m^2) given subcutaneously (SC) daily on Days 1-5 in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 6 total cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Beyond 6 cycles, treatment should continue as long as the participant continues to benefit. BSC should be given according to standard and institutional practice.

Treatment Choice (TC): Before randomization, the investigator will assign each participant to one of the following TC options:

Low dose cytarabine (LDAC) given as 20 mg/m^2 SC or intravenously (IV) once daily for 14 days in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 4 cycles in the absence of disease progression or unacceptable toxicity.
Standard Intensive Chemotherapy (IC) of a 7+3 regimen: given as cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and an anthracycline given as per institutional standard practice such as daunorubicin (45-60 mg/m^2/day), or idarubicin (9-12 mg/m^2/day), or mitoxantrone (8-12 mg/m^2/day) by intravenous infusion for 3 days.
Best Supportive Care (BSC) only: given according to standard and institutional practice. BSC includes, but is not limited to blood transfusions (Red blood cells [RBCs] or platelets), growth factors including erythropoiesis stimulating agents (ESA), granulocyte stimulating factors (GSFs), iron chelating therapy, and broad-spectrum antibiotics and/or antifungals.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Adult participants ≥18 years of age who are able to understand and comply with study procedures and provide written informed consent before any study-specific procedure.
Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification.
Performance status (ECOG) of 0-2.

Previously treated MDS or CMML, defined as prior treatment with at least one hypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or high risk MDS or CMML whose disease progressed or relapsed as follows:

Participant received HMA for at least 6 cycles and was still transfusion dependent.
Participant received HMA for at least 2 complete cycles and had disease progression prior to Cycle 6 defined as

i. ≥50% increase in bone marrow blasts from pre-HMA-treatment levels or from nadir post-HMA-treatment levels to >5% (for participants with pretreatment or nadir blasts ≤5%) or to >10% (for participants with pretreatment or nadir blasts >5%), and/or ii. Transfusion dependent and ≥2 gram/deciliter (g/dL) reduction of Hgb from pre-HMA-treatment levels.

Other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy, hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant (HCT) are allowed.

Participants must have either:

Bone marrow blasts >5% at randomization, OR
Transfusion dependence, defined as having had transfusion (in the setting of active disease) of 2 or more units of RBC or platelets within 8 weeks prior to randomization.
Creatinine clearance or glomerular filtration rate ≥30 milliliter/minute (mL/min) estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration).
Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential and men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child (a) while receiving treatment with guadecitabine and for at least 3 months after completing treatment and (b) while receiving treatment with LDAC or IC and for at least 6 months after completing treatment or for the duration specified in local prescribing information, whichever is longer.

Exclusion Criteria:

Participants who have been diagnosed as having AML with peripheral blood or bone marrow blasts of ≥20%.
Participants who may still be sensitive to repeated treatment with decitabine or azacitidine such as participants who had response to prior decitabine or azacitidine treatment, but relapsed >6 months after stopping treatment with these agents.
Prior treatment with guadecitabine.
Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
Treated with any investigational drug within 2 weeks of the first dose of study treatment.
Total serum bilirubin >2.5 × upper limit of normal (ULN) (except for participants with Gilbert's Syndrome for whom direct bilirubin is <2.5×ULN), or liver cirrhosis or chronic liver disease Child-Pugh Class B or C.
Known active HIV, HBV, or HCV infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol.
Refractory congestive heart failure unresponsive to medical treatment, active infection resistant to all antibiotics, or advanced non-MDS associated pulmonary disease requiring >2 liters per minute oxygen.
Life expectancy of less than one month
Participants with TP53 mutations

Study is for people with:

Myelodysplastic Syndrome

Phase:

Phase 3

Estimated Enrollment:

417

Study ID:

NCT02907359

Recruitment Status:

Completed

Sponsor:

Astex Pharmaceuticals, Inc.

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 33 Locations for this study

See Locations Near You

City of Hope
Duarte California, 91010, United States
Desert Hematology Oncology Medical Group, Inc.
Rancho Mirage California, 92270, United States
Cancer Specialists of North Florida
Fleming Island Florida, 32003, United States
Mount Sinai Medical Center
Miami Beach Florida, 33140, United States
Rush University Medical Center
Chicago Illinois, 60612, United States
North Shore Medical Center
Evanston Illinois, 60201, United States
Franciscan Health Indianapolis
Indianapolis Indiana, 46237, United States
University of Maryland
Baltimore Maryland, 21201, United States
University of Michigan Cancer Center
Ann Arbor Michigan, 48109, United States
John Theurer Cancer Center
Hackensack New Jersey, 07601, United States
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
Weill Cornell Medical College
New York New York, 10065, United States
Stony Brook University Medical Center
Stony Brook New York, 11794, United States
Duke Cancer Center
Durham North Carolina, 27705, United States
Penn State Milton S. Hershey Medical Center
Hershey Pennsylvania, 17033, United States
Fox Chase Cancer Center
Philadelphia Pennsylvania, 19111, United States
Medical University of South Carolina
Charleston South Carolina, 29425, United States
Bon Secours Saint Francis Hospital
Greenville South Carolina, 29607, United States
University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States
Swedish Cancer Institute
Seattle Washington, 98104, United States
Fred Hutchinson Cancer Research Center
Seattle Washington, 98109, United States
West Virginia University Mary Babb Randolph Cancer Center
Morgantown West Virginia, 26506, United States
Ziekenhuis Netwerk Antwerpen Stuivenberg
Antwerp , , Belgium
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende
Brugge , , Belgium
Grand Hôpital de Charleroi - Notre Dame
Charleroi , , Belgium
Tom Baker Cancer Center
Calgary Alberta, T2N 4, Canada
University of Alberta Hospital
Edmonton Alberta, T6G 2, Canada
Royal Victoria Regional Health Centre
Barrie Ontario, L4M 6, Canada
Juravinski Cancer Centre
Hamilton Ontario, L8V 1, Canada
Princess Margaret Hospital
Toronto Ontario, M5G 2, Canada
Burnaby Hospital
Burnaby , , Canada
Moncton Hospital
Moncton , , Canada
Maisonneuve-Rosemont Hôpital Service d'Hematologie et d'Oncologie Medicale
Montréal , , Canada
Saskatchewan Cancer Agency
Regina , , Canada
Fakultní nemocnice Brno
Brno , , Czechia
Fakultni Nemocnice Hradec Králové
Hradec Králové , , Czechia
Fakultní nemocnice Ostrava
Ostrava , , Czechia
Onkologická klinika Všeobecná fakultní nemocnice v Praze a 1
Praha 2 , , Czechia
Fakultní Nemocnice Královské Vinohrady
Praha , , Czechia
Aalborg Universitetshospital
Aalborg , , Denmark
Aarhus Universitetshospital
Aarhus , , Denmark
Rigshospitalet
Copenhagen , , Denmark
Odense University Hospital
Odense , , Denmark
Centre Hospitalier Universitaire
La Tronche , , France
Hôpital Dupuytren
Limoges , , France
GHR Mulhouse Sud-Alsace
Mulhouse Cedex , , France
Hôpital Hôtel-Dieu
Nantes , , France
Centre Antoine Lacassagne
Nice , , France
Hôpital Saint Louis
Paris , , France
Centre Hospitalier Lyon Sud
Pierre-Bénite , , France
Centre Hospitalier Universitaire de Toulouse
Toulouse , , France
Städtisches Klinikum Braunschweig
Braunschweig , , Germany
Marien Hospital Düsseldorf
Düsseldorf , , Germany
Universitaetsklinikum Freiburg
Freiburg , , Germany
Universitätsklinikum Halle
Halle , , Germany
Universitätsklinikum Ulm
Ulm , , Germany
Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria
Alessandria , , Italy
Azienda Ospedaliero Universitaria Careggi
Firenze , , Italy
Azienda Ospedaliera Universitaria San Martino
Genova , , Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milano , , Italy
AORN A. Cardarelli
Napoli , , Italy
Azienda Ospedaliera Universitaria-Maggiore della Carità di Novara
Novara , , Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Pesaro , , Italy
Ospedale S. Eugenio
Roma , , Italy
NHO Nagoya Medical Center
Nagoya-shi Aichi, , Japan
Narita Red Cross Hospital
Narita Chiba, , Japan
University of Fukui Hospital
Yoshida Fukui, , Japan
Chugoku Central Hospital
Fukuyama-shi Hiroshima, , Japan
Tokai University Hospital
Isehara Kanagawa, , Japan
Kitasato University Hospital
Sagamihara-shi Kanagawa, , Japan
Yokohama Municipal Citizen's Hospital
Yokohama Kanagawa, , Japan
Nagasaki University Hospital
Nagasaki Nagasaki-shi, , Japan
Kansai Medical University Hirakata
Hirakata Osaka, , Japan
Kindai University Hospital
Osakasayama-shi Osaka, , Japan
Saitama Medical Center
Kawagoe Saitama, , Japan
Nippon Medical School Hospital
Bunkyō-Ku Tokyo, , Japan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Koto Tokyo, , Japan
NTT Medical Center Tokyo
Shinagawa Tokyo, , Japan
National Hospital Organization Disaster Medical Center
Tachikawa Tokyo, , Japan
National Hospital Organization Kyushu
Fukuoka , , Japan
Fukushima Medical University
Fukushima , , Japan
Gifu Municipal Hospital
Gifu , , Japan
National Hospital Organization Kumamoto Medical Center
Kumamoto , , Japan
Japanese Red Cross Kyoto Daini Hospital
Kyoto , , Japan
University Hospital-Kyoto Prefectural University of Medicine
Kyoto , , Japan
Yamagata University Hospital
Yamagata , , Japan
Seoul National University Hospital
Seoul , 03080, Korea, Republic of
Severance Hospital, Yonsei University Health System
Seoul , 03722, Korea, Republic of
Asan Medical Center
Seoul , 05505, Korea, Republic of
Samsung Medical Center
Seoul , 06351, Korea, Republic of
Seoul Saint Mary's Hospital
Seoul , 137-7, Korea, Republic of
Ulsan University Hospital
Ulsan , 44033, Korea, Republic of
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin , , Poland
Instytut Hematologii i Transfuzjologii
Warszawa , , Poland
Samodzielny Publiczny Centralny Szpital Kliniczny
Warszawa , , Poland
Hospital General Universitario de Alicante
Alicante , , Spain
Hospital Universitari Germans Trias i Pujol
Badalona , , Spain
Fundació Hospital de la Santa Creu i Sant Pau
Barcelona , , Spain
Hospital Universitario Vall d'Hebron
Barcelona , , Spain
Hospital San Pedro de Alcantara
Cáceres , , Spain
Hospital de León
León , , Spain
Hospital General Universitario Gregorio Marañon
Madrid , , Spain
Hospital Universitario 12 de Octubre
Madrid , , Spain
Hospital Universitario Ramón Y Cajal
Madrid , , Spain
Hospital Universitario de Salamanca
Salamanca , , Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia , , Spain
Sahlgrenska Universitetssjukhuset, Östra sjukhuset
Göteborg , , Sweden
Universitetssjukhuset Örebro
Örebro , , Sweden
Medway NHS Foundation Trust
Gillingham , , United Kingdom
The Leeds Teaching Hospitals NHS Trust
Leeds , , United Kingdom
Chelsea and Westminster Hospital NHS Foundation Trust
London , , United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham , , United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Myelodysplastic Syndrome

Phase:

Phase 3

Estimated Enrollment:

417

Study ID:

NCT02907359

Recruitment Status:

Completed

Sponsor:


Astex Pharmaceuticals, Inc.

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.